The proposed studies are designed to elucidate the neuroendocrine basis of sexual responsiveness in female mammals. The importance of various CNS sites in mediating the stimulating effects of estrogen and progesterone and estrous behavior will be investigated. Emphasis will be placed on studying the mechanisms by which the ovarian steroids produce their effects and the pathways by which estrogen and progesterone sensitive sites and interact and exert their influence over structures regulating sexual reflexes. The intensity of receptive behavior will be measured in ovariectomized female rats after treatment with exogenous ovarian hormones. Various procedures will superimposed on this treatment paradigm in attempts to modify the behavior normally induced under optimal conditions. These procedures will include infusing pharmacological compounds with either (a) anti-estrogenic, (b) RNA synthesis inhibiting or (c) protein synthesis inhibiting properties directly into localized sites within the diencephalon. The extent that each of these classes of agents can disrupt sexual responsiveness when administered at different brain sites and at different times with respect to estrogen treatment can be determined. Experiments are designed to clarify the biochemical mechanisms regulating reproductive behavior. In a related series of studies, procedures will be utilized to determine the effects of hypothalamic lesions on sensitivity of the estrous behavior mechanism to progesterone, independent of effects of estrogen processes. These experiments will be extended by making use of knife cut techniques for severing fiber connections within the brain while minimizing extensive damage to critical nuclear groups. These experiments will permit us to analyse the neural connections by which putative estrogen and progesterone responsive areas interact, and the pathways by which these sites connect with other components of the sexual reflex mechanism.